Functional connectivity between medial pulvinar and cortical networks as a predictor of arousal to noxious stimuli during sleep.

The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre-stimulus functional connectivity between sensory and higher-level cortical areas. In addition, stimuli inducing arousal also trigger a widespread EEG response reflecting the coordinated activation of a large cortical network. Since functional connectivity between distant cortical areas is thought to be underpinned by trans-thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra-cortical and intra-thalamic signals were analysed in 440 iEEG segments during nocturnal sleep in 8 epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 seconds before and one second after the nociceptive stimulus, and contrasted according to the presence or absence of an arousal EEG response. Pre- and post-stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (REM) sleep. Thalamo-cortical enhancement in coherence involved both sensory and higher-level cortical networks and predominated in the pre-stimulus period. The association between pre-stimulus widespread increase in thalamo-cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans-thalamic transfer of information between cortical areas.